Wnt pathway component LEF1 mediates tumor cell invasion and is expressed in human and murine breast cancers lacking ErbB2 (her-2/neu) overexpression

Nguyen, Anthony; Rosner, Andrea; Milovanović, Tatjana; Hope, Christopher; Planutis, Kestutis; Saha, Bodhisattwa; Chaiwun, Benjaporn; Lin, Fritz; Imam, S. A.; Marsh, J. Lawrence; Holcombe, Randall F.

doi:10.3892/ijo.27.4.949

Cited by 34 publications

(39 citation statements)

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“…TCF/LEF-1 is a downstream regulator of the Wnt signaling pathway, which has been shown to correlate with ER status in tumors and, interestingly, has been shown to inhibit tumor cell invasion in Matrigel assays when overexpressed (38). Furthermore, Lef-1 knockout mice fail to develop mammary glands (24), confirming a role for LEF-1 in mammary cells and breast cancer.…”

Section: Discussionmentioning

confidence: 85%

Nkx3-1 and LEF-1 Function as Transcriptional Inhibitors of Estrogen Receptor Activity

et al. 2008

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Estrogen receptor (ER)-associated cofactors and cooperating transcription factors are one of the primary components determining transcriptional activity of estrogen target genes and may constitute potential therapeutic targets. Recent mapping of ER-binding sites on a genome-wide scale has provided insight into novel cooperating factors based on the enrichment of transcription factor motifs within the ERbinding sites. We have used the ER-binding sites in combination with sequence conservation to identify the statistical enrichment of Nkx and LEF motifs. We find that Nkx3-1 and LEF-1 bind to several ER cis-regulatory elements in vivo, but they both function as transcriptional repressors of estrogen signaling. We show that Nkx3-1 and LEF-1 can inhibit ER binding to chromatin, suggesting competition for common chromatin-binding regions. These data provide insight into the role of Nkx3-1 and LEF-1 as potential regulators of the hormone response in breast cancer. [Cancer Res 2008;68(18):7380-5]

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Section: Discussionmentioning

confidence: 85%

Nkx3-1 and LEF-1 Function as Transcriptional Inhibitors of Estrogen Receptor Activity

et al. 2008

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“…TCF/ LEF and nuclear b-catenin expression correlate with invasiveness in colon carcinoma and over-expression induces invasion in model cell lines (Nguyen et al, 2005). Like both Ets-1 and NF-kB, TCF/LEF has been shown to synergistically regulate MMP genes with AP-1 via direct interaction with c-Jun (Rivat et al, 2003).…”

Section: Tcf/lefmentioning

confidence: 99%

Transcription factors control invasion: AP-1 the first among equals

et al. 2006

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“…It has been reported to be essential for EMT processes during gastrulation, somitogenesis, limb development, delamination and fate specification of neural crest cells and palate fusion [Oosterwegel et al, 1993;Takeda et al, 2000;Skromne and Stern, 2001;Nawshad and Hay, 2003;Schmidt et al, 2004], and its activator ␤ -catenin is critical for heart cushion formation [Liebner et al, 2004]. Besides these roles during development, an increasing number of studies reports either upregulation or aberrant activation of LEF-1 during cancer progression in various organs including colon, skin, breast, blood and lymph nodes [Rubinfeld et al, 1997;Brabletz et al, 2001;Li et al, 2004;Waterman, 2004;Nguyen et al, 2005;Simon et al, 2005;Howe and Bromidge, 2006] and suggest LEF-1 to play a role downstream of ␤ -catenin also in lung, kidney, cervical and ovarian carcinomas [Ueda et al, 2001].…”

Section: ␤ -Catenin/lef In Developmentmentioning

confidence: 99%

β-Catenin/LEF-1 Signalling in Breast Cancer – Central Players Activated by a Plethora of Inputs

Gebeshuber¹,

Sladecek²,

Grünert³

2007

Cells Tissues Organs

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Although the role of Wnt signalling in breast cancer is far from being fully understood, in the last years its importance has been reported frequently. Besides stimulation by canonical Wnt signalling, the downstream effectors β-catenin and the transcriptional modulators of the T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) family can also be activated by other inputs including the TGF-β pathway. Wnt and TGF-β signalling are both major signal transduction pathways, which provide important cues during development and tumor progression. However, particularly TGF-β has a complicated influence on oncogenesis, which ranges from suppressive to promoting activity. Signalling pathways activated in parallel with TGF-β might determine the oncogenic influence, and therefore place signals cooperating with TGF-β into the limelight. During early development Wnt and TGF-β signalling collaborate extensively. Here we provide an overview of the known interactions of Wnt with TGF-β signalling in development and metastasis, particularly in breast cancer. We want to focus on the Wnt-activated transcription factor complex β-catenin/LEF-1, its upstream activators, its downstream targets and consequences on the cellular level in response to β-catenin/LEF-1 activation.

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Wnt pathway component LEF1 mediates tumor cell invasion and is expressed in human and murine breast cancers lacking ErbB2 (her-2/neu) overexpression

Cited by 34 publications

References 0 publications

Nkx3-1 and LEF-1 Function as Transcriptional Inhibitors of Estrogen Receptor Activity

Nkx3-1 and LEF-1 Function as Transcriptional Inhibitors of Estrogen Receptor Activity

Transcription factors control invasion: AP-1 the first among equals

β-Catenin/LEF-1 Signalling in Breast Cancer – Central Players Activated by a Plethora of Inputs

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